Serum enzymes in head and neck cancer. IV: 5-nucleotidase

Lal, Harbans; Kumar, L.; Kohli, G. S.; Sharma, Anisha; Goel, H. C.

doi:10.1017/s0022215100108436

Cited by 8 publications

(5 citation statements)

References 9 publications

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“…It is very well established that CD39 and CD73 promote the tumor mass progression in different kinds of cancer [17] and that they act by modulating the immune system to ensure tumor progression [16]. Previous studies demonstrated a high CD73 activity in blood serum of patients with head and neck cancer [21] and with intracranial neoplasias [22]. Clayton and collaborators have shown that the supernatant of different kinds of tumor cells secreted exosomes with CD39 and CD73 activity, which modulated the isolated T-cells [19].…”

Section: Introductionmentioning

confidence: 99%

Hydrolysis of ATP, ADP, and AMP is increased in blood plasma of prostate cancer patients

Gardani

Cappellari

Souza

et al. 2019

Purinergic Signalling

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Prostate cancer is among the major malignancies that affect men around the world. Adenine nucleotides are important signaling molecules that mediate innumerous biological functions in pathophysiological conditions, including cancer. These molecules are degraded by several ectoenzymes named ectonucleotidases that produce adenosine in the extracellular medium. Some of these ecto-enzymes can be found in soluble in the blood stream. Thus, the present study aimed to evaluate the hydrolysis of adenine nucleotides (ATP, ADP, and AMP) in the plasma blood of patients with prostate cancer. Peripheral blood samples were collected, and questionnaires were filled based on the clinical data of the medical records. The nucleotide hydrolysis was performed by Malachite Green method using ATP, ADP, and AMP as substrates. Plasma from prostate cancer patients presented an elevated hydrolysis of all nucleotides evaluated when compared to healthy individuals. NTPDase inhibitor (ARL67156) and the alkaline phosphatase inhibitor (levamisole) did not alter ATP hydrolysis. However, AMP hydrolysis was reduced by the CD73 inhibitor, APCP, and by levamisole, suggesting the action of a soluble form of CD73 and alkaline phosphatase. On microvesicles, it was observed that there was a low expression and activity of CD39 and almost absent of CD73. The correlation of ATP, ADP, and AMP hydrolysis with clinic pathological data demonstrated that patients who received radiotherapy showed a higher AMP hydrolysis than those who did not, and patients with lower clinical stage (CS-IIA) presented an elevated ATP hydrolysis when compared to those with more advanced clinical stages (CS-IIB and CS-III). Patients of all clinical stages presented an elevated AMPase activity. Therefore, we can suggest that the nucleotide hydrolysis might be attributed to soluble ecto-enzymes present in the plasma, which, in a coordinate manner, produce adenosine in the blood stream, favoring prostate cancer progression.

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Section: Introductionmentioning

confidence: 99%

Hydrolysis of ATP, ADP, and AMP is increased in blood plasma of prostate cancer patients

Gardani

Cappellari

Souza

et al. 2019

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…Earlier studies in head and neck cancer demonstrated that the serum expression of CD73 was increased in patients with cancer compared with healthy subjects and its enzymatic activity was associated with the stage of cancer. 26 Elevated blood levels of soluble CD73 were found in patients with colorectal cancer, prostate cancer and cervical cancer. [27][28][29] Recently published data from patients with colorectal cancer liver metastases show that high levels of soluble CD73 expression are associated with shorter survival.…”

Section: Discussionmentioning

confidence: 99%

Serum CD73 is a prognostic factor in patients with metastatic melanoma and is associated with response to anti-PD-1 therapy

Turiello

Capone

Giannarelli

et al. 2020

J Immunother Cancer

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BackgroundInhibitors of immune checkpoint programmed cell death protein 1 (PD-1) receptor on T cells have shown remarkable clinical outcomes in metastatic melanoma. However, most patients are resistant to therapy. Production of extracellular adenosine, via CD73-mediated catabolism of AMP, contributes to suppress T-cell-mediated responses against cancer. In this study, we analyzed the expression and activity of soluble CD73 in sera of patients with melanoma undergoing anti-PD-1± cytotoxic T-lymphocyte-associated antigen 4 therapy.MethodsSoluble CD73 expression and activity were retrospectively analyzed in serum of a total of 546 patients with melanoma from different centers before starting treatment (baseline) with anti-PD-1 agents, nivolumab or pembrolizumab, and compared with those of 96 healthy subjects. The CD73 activity was correlated with therapy response and survival of patients.ResultsPatients with melanoma show significantly higher CD73 activity and expression than those observed in healthy donors (p<0.0001). Elevated pretreatment levels of CD73 activity were associated with non-response to therapy with nivolumab or pembrolizumab. During treatment, levels of soluble CD73 activity remain unchanged from baseline and still stratify clinical responders from non-responders. High levels of serum CD73 enzymatic activity associate with reduced overall survival (OS; HR=1.36, 95% CI 1.03 to 1.78; p=0.03) as well as progression-free survival (PFS; HR=1.42, 95% CI 1.13 to 1.79, p=0.003). Further, the multivariate Cox regression analysis indicates that serum CD73 activity is an independent prognostic factor besides serum lactate dehydrogenase levels and the presence of brain metastases for both OS (p=0.009) and PFS (p=0.001).ConclusionOur data indicate the relevance of serum CD73 in patients with advanced melanoma receiving anti-PD-1 therapy and support further investigation on targeting CD73 in combination with anti-PD-1 antibodies.

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“…Since a soluble form of human CD73 was identified (Thompson et al, 1987;Coade and Pearson, 1989), many studies were settled to understand the role of this form in inflammatory and tumor processes. In 1989, Lal and colleagues reported that CD73 expression in serum of head and neck cancer patients was higher than that in healthy subjects (Lal et al, 1989). Interestingly, the enzymatic activity increased with the advancement in the stage of cancer (Lal et al, 1989).…”

Section: Soluble Cd73 In Cancer Patientsmentioning

confidence: 99%

“…In 1989, Lal and colleagues reported that CD73 expression in serum of head and neck cancer patients was higher than that in healthy subjects (Lal et al, 1989). Interestingly, the enzymatic activity increased with the advancement in the stage of cancer (Lal et al, 1989). Of note, Lehto and Sharom in 1998 observed that the soluble form of CD73 is enzymatically more active than the membrane-bound variant (Lehto and Sharom, 1998).…”

Section: Soluble Cd73 In Cancer Patientsmentioning

confidence: 99%